Organ Banking: From Impossible to Slightly Less Impossible

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Organ Banking: From Impossible to Slightly Less Impossible

Every time an organ donor dies, a timer starts counting down. Once a surgeon removes a kidney from a body, it can only survive for about 36 hours. Livers, four to 16 hours; hearts, just three to five.

Today, if an organ doesn't make it to an acceptable donor by the time the clock runs out, it's discarded—useless. And that's a travesty. Over 120,000 people in the US sit on the transplant waiting list every year—yet in 2014, only 29,532 of individuals received an organ. Every day, 21 people die while waiting on that list.

But there's a way to add more sand to the hourglass: organ banking. If scientists can find a way to lengthen organs' shelf life, they could be set aside, creating a stockpile for when patients need them. Doctors could also take the time to repair tissue, turning more organs into viable donations. And if a transplant didn't have to happen immediately, a recipient's immune system could be slowly acclimated to the new organ's cells, making their body less likely to reject it.

Recognizing banking's potential, the US Department of Defense recently awarded $3.5 million worth of grants to several startups that are trying to finally figure out how to preserve organs. One method looks to essentially freeze-dry them for quick, convenient storage; the other wants to change how their cells and tissues operate, nudging them into a hibernation of sorts. The former would be faster, and the latter would probably be safer—but both methods have their obstacles.

Cryopreservation

The most popular organ-preserving method being researched is cryopreservation—the deep freeze of living organisms or organic material, usually with liquid nitrogen. Right now, cryopreservation is tough, for the same reason that previously frozen meat doesn't taste as good as fresh stuff: Ice crystals. When crystals form, they damage cells and tissues, making an organ impossible to transplant.

The solution—at least for human tissue—is to freeze and unfreeze the organ fast enough to keep ice from collecting on the surface. Additionally, when you’re bringing an organ back to body temperature, uniform heating is essential to avoid thermal stress that could crack the tissue (like an ice cube dropped in lukewarm water).

The biggest milestone in cryopreservation came in 2005, when Greg Fahy successfully cooled a rabbit kidney down to a vitrified form—a glass-like form of stasis. Vitrification is an intensely fast process that avoids ice-crystal formation—it's the same way doctors preserve human egg cells and embryos. Many hoped this breakthrough would light the path towards whole organ preservation. But Fahy couldn't figure out how to re-animate the organs without cracking from the thermal stress of heating.

John Bischof, an nanoengineer at the University of Minnesota, thinks he's found a solution to that problem. He proposes dropping vitrified organs into cryopreservant—basically, anti-freeze—that contains magnetic nanoparticles. When they're exposed to RF waves, the nanoparticles start vibrating, heating up the solution by over 100 degrees Celsius per minute and warming the organ from within. Bischof and his colleagues have shown their wiggling nanoparticles work in different solutions and prevents ice-crystal formation and cracking-–but only in rodent cells and tissues.

Other researchers are trying to avoid ice formation by freezing organs—without technically freezing them. Mehmet Toner, a bioengineer at Harvard, is working to supercool tissues, lowering the temperature of the cells so quickly that the water in them remains liquid even below water's freezing point. Labs at UC Berkeley and the United States Military Academy at West Point are working on something similar called isochoric cooling, which lowers temperatures in a preservation chamber by increasing pressure while retaining the same volume.

But despite all the artificial chemicals and tweaks to temperature that scientists throw at organs, these scientists might never be able to freeze and reheat an organ without creating some kind of damage. So other scientists are looking to nature for inspiration, and learning to apply what other animals do to human organ preservation.

Freezing time

Cryopreservation is a real technology that's a favorite plot device in movies. But the other main strategy being considered to preserve organs is straight-up science fiction. Instead of putting a kidney or heart in a subzero deep freeze, Carleton University’s Ken Storey is investigating how to "stop biological time." He wants to turn an organ off like it's hibernating, and turn it back on when it's ready to be transplanted.

Most vertebrates with a backbone "can turn themselves off completely, live in suspended animation, and come back to life," says Storey. He specifically takes his cues from the biological mechanisms that primates like ground-tailed squirrels and fat-tailed dwarf lemurs use to hibernate.

That's easier said than done. Most mammals that hibernate do so when changes in the environment activate cell pathways that start to shut down the energy components that break down fats and sugars for fuel, and DNA-related activity that leads to the creation of new proteins and destruction of old ones. But in humans, these pathways can’t be turned off—they just shift in a different direction that keeps them functioning, or the cells will start undergoing a programmed process of death called apoptosis.

Storey thinks if he can turn those pathways can be shut off without causing apoptosis, he can artificially induce a state of suspended animation in an organ. And what about bringing the organ back to life? "You just have to reverse what you did before," he says.

One of the keys to achieving this, says Storey, is identifying the one to two percent of cell functions that stay on to keep the body alive during stasis. While they’ve been able to pinpoint how these genes avoid the factors that would normally silence them, they have still yet to identify what they are and why they’re essential. Although Storey and his lab have made a lot of progress in figuring all of this out at the cellular level, they’re still nowhere close to being able to get an entire organ to move into suspended animation.

Low-tech solutions

Which brings up the problem that plagues all of these different research projects—they're in their infancy. Most of the methods have only been tested in animals or very basic human cell lines. No one is close to getting an entire human organ to survive outside the body for several days on end.

And many working to address organ shortages are skeptical about shifting resources toward science and tech research. Organ banking could raise new ethical questions. According to Northeastern University law professor Kara Swanson, who's written about the legal debates behind the property of the human body, the ability to begin banking organs will probably raise debates on whether society will start offering monetary compensation for organs (which is currently illegal), and turn body parts into something like medication you can buy over the counter.

Waitlist Zero, an organization working to end shortages in kidney donation, thinks the focus should be on increasing living donor lists—persuading more people to donate organs they can live without. “If only 0.06 percent of Americans donated [a kidney], we could end the kidney shortage tomorrow,” says Josh Morrison, the executive director of Waitlist Zero. "Pursuing living donation strategies (or other strategies to increase organ donation today) should not come at the expense of scientific investment for the future."

Alexandra Glazier, the president and CEO of the New England Organ Bank, also lists other ways to tackle organ shortages. Though she is optimistic about the role new science and tech advancements will play, she thinks there are other avenues to pursue as well—such as the increasing the pool of clinically-acceptable donors by easing restrictions against individuals with certain comorbidities or infections.

In the end, both strategies may be necessary to help the 120,000-plus Americans waiting for a new organ. Every year, 4,000 healthy organs are discarded because a good match can't be found in time, while over 6,000 people on the transplant waiting list die. So organ banking may be able to put a dent in those deaths—but it will take increased donation rates to prevent the rest.